A First: Human Clinical Trial Assessing Gene Therapy for Alzheimer’s Disease

Billions of dollars have been spent in research over decades, resulting in only two therapies that treat symptoms of Alzheimer’s disease (AD). There are no approved methods that diminish the effects of Alzheimer’s. It is a disease that affects over five million Americans.

According to a recent article in Neuroscience News, UCSD researchers, led by Professor Mark Tuszynski, have initiated the first-in-human clinical trial assessing the efficacy and safety of a gene therapy that delivers a critical protein to the brains of Alzheimer’s patients. The Phase 1 clinical trial will also include people with mild cognitive impairment (MCI), which is often a precursor to dementia.

The animal models are genetically engineered amyloid mice. The mice are structured to develop amyloid plaques (clusters of amyloid proteins) by way of an inherited mutation. The mutation occurs in the gene that encodes the amyloid precursor protein.

Professor Tuszynski and his team had previously reported on the reversal and prevention of the death of brain cells and degeneration in laboratory animals. The researchers found that when they delivered brain-derived neurotrophic factor (BDNF) to the area in the brain initially affected by Alzheimer’s disease, they could re-establish connections and prevent cell degeneration.

BDNF comes into play through the BDNF gene which sends out instructions for the creation of a protein called, similarly, brain-derived neurotrophic factor. BDNF is produced during our lifetime in the memory center of the brain. The first signs of AD occur in the memory center as short-term loss of memory.

BDNF is a Challenge

According to the researchers, working with BDNF, due to its size, is a challenge. BDNF is not able to pass through the blood-brain barrier. The solution has been to use an adeno-associated virus (AAV2). The virus is rendered harmless and carries the BDNF gene, which is injected into various areas of the brain. The goal is to produce BDNF in cells near the targeted areas. It is critical to administer controlled injections, as circulating BDNF may result in seizures or other adverse effects.

The Phase I Clinical Trial

The trial is slated for three years and will involve twelve people who have either Alzheimer’s disease or MCI. The participants will receive AAV2-BDNF. The second cohort of twelve people will be evaluated as a control group during the three-year period.

The trial will be the first human assessment of AAV2-BDNF. Professor Tuszynski noted that gene therapy has been tested on multiple diseases since 1980. Alzheimer’s requires new thinking and a new approach to treatments. Gene therapy may be the answer.

Professor Tuszynski commented that the researchers intend to continue along the lines of recent gene therapy success against other diseases. He noted that BDNF therapy is not like current AD therapies as BDNF is capable of slowing cell loss, rebuilding brain circuits, and improving cell function.

He concluded the interview by expressing optimism towards an entirely new approach for AD and MCI patients.

Details of the referenced clinical trial may be found here.

Rose Duesterwald

Rose Duesterwald

Rose became acquainted with Patient Worthy after her husband was diagnosed with Acute Myeloid Leukemia four years ago. He was treated with a methylating agent While he was being treated with a hypomethylating agent, Rose researched investigational drugs being developed to treat relapsed/refractory AML.

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